Our laboratory program has continued to pursue investigations directed at understanding the molecular mechanisms underlying transformation and tumorigenesis induced by polyoma virus, while expanding our investigation of the molecular basis of several important questions in pediatric oncology. Experiments focused on the study of oncogenic transformation induced by polyoma virus include: 1) Characterization of a complex between the polyoma virus transforming gene product, middle T antigen, and the cellular proto-oncogene, c-src, in polyoma infected and polyoma transformed cells; 2) Demonstration of a significant increase in the specific activity of c-src tyrosyl kinase activity in the species of c-src which is physically associated with polyoma middle T antigen in cells transformed by polyoma virus; 3) Demonstration of enhanced c-src tyrosyl kinase activity specifically mediated by polyoma middle T antigen prior to the physical association of c-src with polyoma middle T antigen; 4) Development of an in vitro assay in which the association of polyoma middle T antigen with c-src can be evaluated; 5) Identification of the c-src kinase activity as the major tyrosyl phosphotransferase in immunoprecipitates of polyoma middle T antigen. Studies directed at better understanding the molecular events important for the malignant characteristics of pediatric tumors include: 1) Characterization of the biologic and cytogenetic features of cell lines established from pediatric solid tumors; 2) Molecular biological evaluation of cell lines from neuroepithelioma and Ewing's sarcoma to elucidate the biologic significance of the rcp(11;22) translocation in these cells; 3) Evaluation of the effect of retinoic acid induced differentiation on the expression of genes important for the malignant phenotype of cell lines from patients with Stage IV neuroblastoma; 4) Development of lines of investigation which will be useful in identifying genes whose function may be biologically significant for the malignant behavior of pediatric neoplasia.